title: Expression of TP53 mutation-associated microRNAs predicts clinical outcome in head and neck squamous cell carcinoma patients.
abstract: BACKGROUND
  TP53 mutation is associated with decreased survival rate in head and neck squamous cell carcinoma (HNSCC) patients. We set out to identify microRNAs (miRNAs) whose expression associates with TP53 mutation and survival in HNSCC.
  
  
  METHODS
  We analyzed TP53 status by direct sequencing of exons 2 through 11 of a prospective series of 121 HNSCC samples and assessed its association with outcome in 109 followed-up patients. We carried out miRNA expression profiling on 121 HNSCC samples and 66 normal counterparts. miRNA associations with TP53 mutations and outcome were evaluated.
  
  
  RESULTS
  A TP53 mutation was present in 58% of the tumors and TP53 mutations were significantly associated with a shorter recurrence-free survival. This association was stronger in the clinical subgroup of patients subjected to adjuvant therapy after surgery. The expression of 49 miRNAs was significantly associated with TP53 status. Among these 49, we identified a group of 12 miRNAs whose expression correlates with recurrence-free survival and a group of 4 miRNAs that correlates with cancer-specific survival. The two groups share three miRNAs. Importantly, miRNAs that correlate with survival are independent prognostic factors either when considered individually or as signatures.
  
  
  CONCLUSIONS
  miRNAs expression associates with TP53 status and with reduced survival after surgical treatment of squamous cell carcinoma of the head and neck.
authors.affiliation: Translational Oncogenomics Unit, Italian National Cancer Institute 'Regina Elena', Rome, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Ganci
authors.forename: A
authors.initials: A
authors.lastname: Sacconi
authors.forename: N
authors.initials: N
authors.lastname: Bossel Ben-Moshe
authors.forename: V
authors.initials: V
authors.lastname: Manciocco
authors.forename: I
authors.initials: I
authors.lastname: Sperduti
authors.forename: L
authors.initials: L
authors.lastname: Strigari
authors.forename: R
authors.initials: R
authors.lastname: Covello
authors.forename: M
authors.initials: M
authors.lastname: Benevolo
authors.forename: E
authors.initials: E
authors.lastname: Pescarmona
authors.forename: E
authors.initials: E
authors.lastname: Domany
authors.forename: P
authors.initials: P
authors.lastname: Muti
authors.forename: S
authors.initials: S
authors.lastname: Strano
authors.forename: G
authors.initials: G
authors.lastname: Spriano
authors.forename: G
authors.initials: G
authors.lastname: Fontemaggi
authors.forename: G
authors.initials: G
authors.lastname: Blandino
mesh_terms: D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000378:metabolism* / Q000401:mortality / Q000628:therapy; D004252:DNA Mutational Analysis; D018572:Disease-Free Survival; D005260:Female; D015870:Gene Expression; D006258:Head and Neck Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000401:mortality / Q000628:therapy; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D015999:Multivariate Analysis; D009154:Mutation; D009364:Neoplasm Recurrence, Local / Q000235:genetics / Q000378:metabolism* / Q000401:mortality / Q000517:prevention & control; D011379:Prognosis; D016016:Proportional Hazards Models; D011446:Prospective Studies; D016896:Treatment Outcome; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*
chemical_list: D035683:MicroRNAs; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53
keywords: HNSCC; TP53 mutation; clinical outcome; microRNA